860 research outputs found
Toward a Functional Definition of a âRare Diseaseâ for Regulatory Authorities and Funding Agencies
AbstractBackgroundThe designation of a disease as ârareâ is associated with some substantial benefits for companies involved in new drug development, including expedited review by regulatory authorities and relaxed criteria for reimbursement. How ârare diseaseâ is defined therefore has major financial implications, both for pharmaceutical companies and for insurers or public drug reimbursement programs. All existing definitions are based, somewhat arbitrarily, on disease incidence or prevalence.ObjectivesWhat is proposed here is a functional definition of rare based on an assessment of the feasibility of measuring the efficacy of a new treatment in conventional randomized controlled trials, to inform regulatory authorities and funding agencies charged with assessing new therapies being considered for public funding.MethodsIt involves a five-step process, involving significant negotiations between patient advocacy groups, pharmaceutical companies, physicians, and public drug reimbursement programs, designed to establish the feasibility of carrying out a randomized controlled trial with sufficient statistical power to show a clinically significant treatment effect.Results and ConclusionsThe steps are as follows: 1) identification of a specific disease, including appropriate genetic definition; 2) identification of clinically relevant outcomes to evaluate efficacy; 3) establishment of the inherent variability of measurements of clinically relevant outcomes; 4) calculation of the sample size required to assess the efficacy of a new treatment with acceptable statistical power; and 5) estimation of the difficulty of recruiting an adequate sample size given the estimated prevalence or incidence of the disorder in the population and the inclusion criteria to be used
Reflecting tidal wave beams and local generation of solitary waves in the ocean thermocline
It is generally accepted that ocean internal solitary waves can arise from the interaction
of the barotropic tide with the continental shelf, which generates an internal tide that in
turn steepens and forms solitary waves as it propagates shorewards. Some field observations,
however, reveal large-amplitude internal solitary waves in deep water, hundreds of
kilometers away from the continental shelf, suggesting an alternative generation mechanism:
tidal flow over steep topography forces a propagating beam of internal tidal wave
energy which impacts the thermocline at a considerable distance from the forcing site
and gives rise to internal solitary waves there. Motivated by this possibility, a simple
nonlinear long-wave model is proposed for the interaction of a tidal wave beam with
the thermocline and the ensuing local generation of solitary waves. The thermocline is
modelled as a density jump across the interface of a shallow homogeneous fluid layer
on top of a deep uniformly stratified fluid, and a finite-amplitude propagating internal
wave beam of tidal frequency in the lower fluid is assumed to be incident and reflected
at the interface. The induced weakly nonlinear long-wave disturbance on the interface is
governed in the far field by an integralâdifferential equation which accounts for nonlinear
and dispersive effects as well as energy loss owing to radiation into the lower fluid. Depending
on the intensity of the incident beam, nonlinear wave steepening can overcome
radiation damping so a series of solitary waves may arise in the thermocline. Sample
numerical solutions of the governing evolution equation suggest that this mechanism is
quite robust for typical oceanic conditions
Screening for malnutrition in emergency laparotomy patients: a comparison of three tools
Introduction:
Malnourished patients undergoing emergency laparotomy are at risk of significant morbidity. The optimum screening tool to identify such patients in practice and research is yet to be determined. This study aims to compare the performance of three nutrition risk tools in predicting time without enteral nutrition in this population.
Methods:
A prospective cohort study (NCT04696367) was conducted across two sites, recruiting patients undergoing National Emergency Laparotomy Audit eligible procedures. Data collected included demographics, diagnosis, procedure and outcomes. Nutrition risk was assessed using three tools: Malnutrition Universal Screening Tool (MUST) score, Nutritional Risk Index (NRI) and Nutritional Risk Score 2002 (NRS-2002). Complications were assessed with the Comprehensive Complication Index. Quality of life was measured at baseline and 5 days postsurgery using EQ-5D-5L.
Results:
A total of 59 patients were recruited. Median age was 69 years. Of the 59 participants, 23 were judged high risk using MUST score, 13 using NRS and 8 using NRI. Median time to restart enteral intake was 7 days (interquartile range 7â14). Time without intake was correlated with increasing score using MUST (r=0.463, p<0.001) and NRS-2002 (r=0.296, p=0.03) but not NRI (r=â0.121, p=0.38). High-risk nutritional groups also had increased length of hospital stay, but not complication scores.
Conclusions:
Patients undergoing emergency laparotomy spend a prolonged time without enteral nutrition. Although all nutritional tools demonstrated some propensity to identify patients at higher risk of needing nutritional support, their performance was variable. Nevertheless, some may be useful in future clinical studies
An Introduction to Data Analysis in Asteroseismology
A practical guide is presented to some of the main data analysis concepts and
techniques employed contemporarily in the asteroseismic study of stars
exhibiting solar-like oscillations. The subjects of digital signal processing
and spectral analysis are introduced first. These concern the acquisition of
continuous physical signals to be subsequently digitally analyzed. A number of
specific concepts and techniques relevant to asteroseismology are then
presented as we follow the typical workflow of the data analysis process,
namely, the extraction of global asteroseismic parameters and individual mode
parameters (also known as peak-bagging) from the oscillation spectrum.Comment: Lecture presented at the IVth Azores International Advanced School in
Space Sciences on "Asteroseismology and Exoplanets: Listening to the Stars
and Searching for New Worlds" (arXiv:1709.00645), which took place in Horta,
Azores Islands, Portugal in July 201
The landscape of gifted and talented education in England and Wales: How are teachers implementing policy?
This is an Author's Accepted Manuscript of an article published in Research Papers in Education, 27(2), 167-186, 2012, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/02671522.2010.509514.This paper explores the evidence relating to how primary schools are responding to the âgifted and talentedâ initiative in England and Wales. A questionnaire survey which invited both closed and open-ended responses was carried out with a national sample of primary schools. The survey indicated an increasing proportion of coordinators, compared with a survey carried out in 1996, were identifying their gifted and talented children as well as having associated school policies. However, the survey also highlighted a number of issues which need addressing if the initiative is to achieve its objective of providing the best possible educational opportunities for children. For example, it was found that a significant number of practitioners were not aware of the existence of the National Quality Standards for gifted and talented education, provided by the UK government in 2007, and the subject-specific criteria provided by the UKâs Curriculum Authority for identification and provision have been largely ignored. The process of identifying children to be placed on the âgifted and talentedâ register seems haphazard and based on pragmatic reasons. Analysis of teachersâ responses also revealed a range of views and theoretical positioning held by them, which have implications for classroom practice. As the âgifted and talentedâ initiative in the UK is entering a second decade, and yet more significant changes in policy are introduced, pertinent questions need to be raised and given consideration
Numerical analysis of the radio-frequency single-electron transistor operation
We have analyzed numerically the response and noise-limited charge
sensitivity of a radio-frequency single-electron transistor (RF-SET) in a
non-superconducting state using the orthodox theory. In particular, we have
studied the performance dependence on the quality factor Q of the tank circuit
for Q both below and above the value corresponding to the impedance matching
between the coaxial cable and SET.Comment: 14 page
Large-scale magnetic fields from inflation in dilaton electromagnetism
The generation of large-scale magnetic fields is studied in dilaton
electromagnetism in inflationary cosmology, taking into account the dilaton's
evolution throughout inflation and reheating until it is stabilized with
possible entropy production. It is shown that large-scale magnetic fields with
observationally interesting strength at the present time could be generated if
the conformal invariance of the Maxwell theory is broken through the coupling
between the dilaton and electromagnetic fields in such a way that the resultant
quantum fluctuations in the magnetic field has a nearly scale-invariant
spectrum. If this condition is met, the amplitude of the generated magnetic
field could be sufficiently large even in the case huge amount of entropy is
produced with the dilution factor as the dilaton decays.Comment: 28 pages, 5 figures, the version accepted for publication in Phys.
Rev. D; some references are adde
A complete 3D numerical study of the effects of pseudoscalar-photon mixing on quasar polarizations
We present the results of three-dimensional simulations of quasar
polarizations in the presence of pseudoscalar-photon mixing in the
intergalactic medium. The intergalactic magnetic field is assumed to be
uncorrelated in wave vector space but correlated in real space. Such a field
may be obtained if its origin is primordial. Furthermore we assume that the
quasars, located at cosmological distances, have negligible initial
polarization. In the presence of pseudoscalar-photon mixing we show, through a
direct comparison with observations, that this may explain the observed large
scale alignments in quasar polarizations within the framework of big bang
cosmology. We find that the simulation results give a reasonably good fit to
the observed data.Comment: 15 pages, 8 figures, significant changes, to appear in EPJ
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